Abstract:

Dysnatremias can be a challenging

diagnosis for pediatric emergency
care providers because patients can
present with vague symptoms but
can quickly develop neurologic sequelae. It is important that emergency care physicians are
knowledgeable about higher risk
populations, clinical presentation,
and possible etiologies to provide
prompt treatment. This article will
present 2 cases with sodium abnormalities and then review the
epidemiology, pathophysiology, and
current management practices for
dysnatremias.

Keywords:
Dysnatremias; hypernatremia;
hyponatremia; cerebral edema;
central pontine myelinosis;
water deficit

Hypernatremia
and
Hyponatremia:
Current
Understanding
and Management
Catherine H. Chung, MD, MPH ,*
Donald Zimmerman, MD

D
*Division of Emergency Medicine,
Childrens Memorial Hospital, Chicago,
IL; Division of Endocrinology, Childrens
Memorial Hospital, Chicago, IL.
Reprint requests and correspondence:
Catherine H. Chung, MD, MPH, Division of
Emergency Medicine, Children's Memorial
Hospital, 2300 Children's Plaza, Chicago,
IL 60614.
cachung@childrensmemorial.org
1522-8401/$ - see front matter
2009 Published by Elsevier Inc.

272

ysnatremias are a relatively common problem in the

pediatric emergency department (ED). If not identified
promptly or managed properly, patients can develop
neurologic sequelae. Infants are at particular risk due to
immature renal function, increased insensible water loss, and their
inability to communicate symptoms or thirst. Hospitalized
children are also at particular risk due to increased incidence of
the syndrome of inappropriate antidiuretic hormone (SIADH), lack
of free access to water, and improper intravenous fluid administration. To appropriately manage dysnatremias, the clinician must
pay particular attention to fluid intake, fluid status (hypovolemia,
euvolemia, hypervolemia), and insensible water losses.

CASE 1
A 3-week-old full-term female infant presents to the ED with a 2day history of weakness, lethargy. and worsening oral intake. The
infant has been exclusively breast-fed; however, milk production
has been minimal, and the patient feeds 5 minutes per breast
every 3 hours. The patient has lost 15% of her birth weight and has
not been urinating well today. Vitals signs on presentation include
the following: temperature 37.5C; heart rate 180; respiratory rate
25; blood pressure 88/P mmHg; and weight 2.7 kg. The physical

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HYPERNATREMIA AND HYPONATREMIA / CHUNG AND ZIMMERMAN VOL. 10, NO. 4 273

examination was remarkable for a depressed fontanelle, weak cry, and capillary refill time of 2
seconds. The electrolyte panel revealed the following: Na 160 mEq/L; K 4 mEq/L; Cl 130 mEq/L; HCO3
10 mEq/L; blood urea nitrogen 29 mg/dL; and
creatinine 0.5 mg/dL.
What is the likely cause of her hypernatremia?
How should it be managed?

Defining Hypernatremia
Hypernatremia is defined by serum Na of more
than 145 mEq/L and is a result of either excess total
body sodium, limited free water intake, or free water
loss1 (Table 1).

Clinical Manifestations
Patients can present with nonspecific signs such as
weight loss, dehydration, lethargy, and weakness. If
severe hypernatremia occurs acutely, the patient can
be at risk for seizures and coma.1 Historical
information and the physical examination can often
highlight the cause of hypernatremia; however,
hyperosmolality in serum (in association with hypernatremia) and dilute urine (urine osmolality b600
mOsm/kg or urine specific gravity b1.016) can help
differentiate diabetes insipidus from other causes.

Epidemiology
Although diarrheal illness is the most common
etiology of hypernatremia, the overall incidence of
diarrhea-associated hypernatremia has been decreasing due to availability and widespread use of
oral rehydration formulas. In a retrospective review
of hospitalized children with hypernatremia, diarrheal illness accounted for only 20% of the cases.2
More recently, case reports of hypernatremia from

TABLE 1. Causes of hypernatremia.

Sodium excess
Concentrated breast milk or formula
Salt ingestion (accidental, seawater, Munchausen by proxy)
Salt water enemas
Hypertonic saline administration
Sodium bicarbonate
Free water deficit
Diarrhea
Increased insensible water loss (fever, tachypnea, premature
infants)
Diuresis (hyperosmolar states)
Poor access to water or blunted sensation of thirst
Diabetes insipidus

concentrated formula, inadequate breast-feeding,

limited access to water for hospitalized patients, and
iatrogenic administration of concentrated saline
solutions have been reported in the literature.2-5
Moritz6 found that 60% of patients with hypernatremia developed it while they were inpatients. In
the case above, the infant has breast-feeding
hypernatremic dehydration. Several hypotheses
for this etiology are proposed in the literature;
however, it seems that in the setting of poor milk
production, breast milk has higher levels of sodium
with little free water.2-5

Neurologic Sequelae
Retrospective analysis of children with hypernatremic dehydration demonstrates significant neurologic
sequelae, including hypertonicity, developmental
delay, seizures, cerebral thrombosis, and cerebral
hemorrhage despite appropriate rate of correction.3,5-7 Secondary complications such as acute
renal failure and disseminated intravascular coagulation have also been reported in some patients.7
The acuity of the onset of hypernatremia, duration
of uncorrected hypernatremia, and comorbidities
(eg, metabolic syndromes and prematurity) result in
higher morbidity and mortality. Mortality from
hypernatremia is estimated at 10% to 16% despite
correct rates of rehydration.5,6,8
In the setting of hypernatremia, water from the
intracellular space will shift to the extracellular space
via osmosis. When this occurs, the brain can acutely
lose 10% to 15% of its volume and separate from the
meninges, resulting in rupture of the cerebral veins.9
Cerebral hemorrhage, venous sinus thrombosis, and
demyelinating disease can occur in the most severe
cases. If hypernatremia slowly evolves over a long
period of time, the clinical presentation and sequelae
are less severe because neurons have the opportunity
to adapt and reestablish intracellular volume. Osmolytes, which consist of amino acids and carbohydrates, will be produced inside neurons to provide a
diffusion gradient to keep water in the intracellular
space. This adaptive process is essential for neuroprotection; however, it can pose a danger if the
hypernatremia is rapidly corrected such that neurons
swell and result in cerebral edema.1

Management
How to best manage the patient's hydration status
with close attention to the rate of sodium correction
can be challenging. Certainly, if the patient is in
hypovolemic shock or has significant hypovolemia,
isotonic saline should be administered at 10 to 20
mL/kg for 1 hour to replenish the intravascular

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volume. To prevent rapid fluid shifts into neurons

and cerebral edema, the remainder of the fluid
deficit should be corrected during a 48- to 72-hour
period, and in clinical circumstances suggesting
chronicity of more than 1 day, serum sodium should
be reduced at a rate no greater than 0.5 mEq/L
per hour.1
There are several methodologies to estimate the
affected child's water and solute deficit.1,9-12 However, the most important point to understand is that
these calculations are merely rough estimations and
that patients will vary in terms of the actual rate of
correction. Therefore, it is imperative to closely
monitor serum electrolytes every 2 to 4 hours to

ensure judicious correction. Figure 1 provides one

example for the calculation of fluid and electrolyte
requirements in a hypernatremic infant.

CASE 2
A 2-week-old full-term female infant with an
unremarkable birth history presents with generalized tonic-clonic seizures. The mother, who is 19
years old, denies any fevers, changes in appetite, or
activity. She states that the infant has been feeding
well with powdered formula, in which she mixes 1
scoop of powder for every 4 oz of water. Vital signs
on presentation include the following: temperature

Figure 1. Fluid and electrolyte management in hypernatremia.

HYPERNATREMIA AND HYPONATREMIA / CHUNG AND ZIMMERMAN VOL. 10, NO. 4 275

36.5C; heart rate 160; respiratory rate 24; blood

pressure 89/P mmHg, and weight 3.2 kg. The infant's
pre-illness weight was 3.5 kg. The physical examination was remarkable for a lethargic, mildly
dehydrated neonate with a weak cry. Capillary refill
was less than 2 seconds. The electrolyte panel
revealed the following: Na 118 mEq/L; K 3.0 mEq/L;
Cl 92; HCO3 18 mEq/L; blood urea nitrogen 17 mg/
dL; creatinine 0.3 mg/dL; and glucose 90 mg/dL.
What is the likely cause of her hyponatremia?
How should it be managed?

Defining Hyponatremia
Hyponatremia is defined by serum Na less than
130 mEq/L and may be a result of excess free water
intake and/or the inability of the kidneys to excrete
free water, or it can be a result of inadequate total
body sodium (due to insufficient intake or to
excessive losses). Sodium levels are also closely
linked to serum osmolality where hyperglycemia
and treatment with mannitol or glycerol can cause
increased osmolality in the extracellular space,
which, in turn, causes efflux of water from the
intracellular to the extracellular space; translocation
of water produces a relative decrease of sodium
compared with water. Finally, severe hyperlipidemia
or hyperproteinemia can cause a substantial portion
of plasma volume to restrict admixture with sodium;
thus, sodium concentrations are normal in the
plasma compartment, which allows sodium entry,
but low in the total plasma volume. Therefore, it is
important to confirm serum/urine osmolarity and to

exclude hyperlipidemia and hyperproteinemia to

differentiate between true hyponatremia versus
pseudohyponatremia (Table 2).

Pathophysiology
When the body is in an intravascularly depleted
state (ie, third spacing or dehydration), antidiuretic hormone is released; this triggers the kidneys to
retain water even if hyponatremia is present. The
preservation of intravascular volume supersedes
the countervailing signal of hyponatremia.13 In the
setting of SIADH, the body retains water from the
overproduction of antidiuretic hormone despite
being euvolemic.
In a hyponatremic state caused by excess free
water, there is an influx of water into the intracellular space, which can cause intracellular edema. In
attempts to minimize cerebral edema, neurons and
endothelial cells will excrete electrolytes, protein,
and carbohydrates to the extracellular space. If
correction with hypertonic fluid occurs too quickly,
endothelial cells in proximity to neuronal processes
rapidly lose water. This loss of cellular water
produces endothelial cell shrinkage, which, in
turn, enlarges the spaces between endothelial
cells. Enlargement of spaces between endothelial
cells changes the blood-brain barrier and allows
myelinotoxic substances such as tumor necrosis
factor and interferon- to cross. Destruction of the
myelin sheath ensues this process; osmotic pontine
myelinosis, also known as central pontine myelinosis, can result in mild to severe neurologic deficits.

Clinical Manifestations
TABLE 2. Causes of hyponatremia. 1
Normal total body water and sodium
Hyperglycemia
Mannitol, glycerol therapy
Increased total body water and sodium
Congestive heart failure
Acute renal failure
Nephrosis
Decreased total body water and sodium
Gastrointestinal losses (diarrhea, emesis)
Renal losses (diuretic, renal tubular acidosis, renal interstitial
disease)
Adrenal causes
Third spacing
Increased total body water and normal sodium
SIADH
Water intoxication
Pseudohyponatremia
Extreme hyperlipidemia or hypoproteinemia

The clinical presentation should greatly assist the

ED physician in diagnosing the cause of hyponatremia. Children with hyponatremic dehydration
manifest signs of dehydration such as low blood
pressure, tachycardia, increased capillary refill
time, dry mucus membranes, and decreased skin
turgor. Children with congestive heart failure,
nephrotic syndrome, or liver dysfunction manifest
signs typical of these conditions, including edema.
Children with hypothyroidism have typical symptoms of decreased energy, constipation, and cold
intolerance and manifest signs including dry and
sallow skin, bradycardia with narrow pulse pressure,
and delayed relaxation phase of the deep tendon
reflexes. Children with adrenal insufficiency have
low energy and may have a history of prostration
with intercurrent illness and hypoglycemic symptoms. Those with primary adrenal insufficiency
have hyperpigmentation of the skin over bony
prominences, in skin creases and of recent scars.

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Children with SIADH frequently have a history of

central nervous system or pulmonary disease or a
history of taking medications that can promote
SIADH such as cyclophosphamide, vincristine,
carbamazepine, haloperidol, or antidepressants.
With the acute onset of hyponatremia, the shift of
water from the extracellular to the intracellular
space can cause cellular edema and may present
with nonspecific signs such as anorexia, lethargy,
and muscle cramps.1 If hyponatremia occurs quickly or if corrected too rapidly, cerebral edema can
ensue, resulting in headache, emesis, mental status

changes, permanent neurologic damage, and death.9

Children are at greater risk for cerebral edema than
are adults because they have higher brain to skull
volume ratio, which means that there is less volume
for cerebral expansion.9

Epidemiology
It is believed that water intoxication and gastroenteritis are the most common causes of hyponatremia in the first few years of life. A retrospective
study of infants presenting with seizures and

Figure 2. Fluid and electrolyte management in hyponatremic dehydration.

HYPERNATREMIA AND HYPONATREMIA / CHUNG AND ZIMMERMAN VOL. 10, NO. 4 277

hyponatremia demonstrated that water intoxication

was the primary cause in 70% of children younger
than 6 months and in 56% of children younger than
2 years.12 Water intoxication is often due to dilution
of powdered formula, as in the case above, usually
by parents who are unaware how to properly mix
formula or by those who try to extend their limited
supplies. There have also been a few case reports of
water intoxication as a manifestation of child
abuse.13-16 The incidence of hyponatremia from
gastroenteritis is unclear. Many recent studies have
focused on iatrogenic hyponatremia of hospitalized
children from hypotonic fluid administration.9,17-22
The incidence of iatrogenic hyponatremia has
been estimated to be equivalent to 1% of hospitalized children.10 There have been 2 case reports
describing the use of D5W in the ED for
resuscitation, both of which resulted in mortality.23 Most of the case reports of death from
iatrogenic hyponatremia have been in healthy
children who received hypotonic fluid postoperatively.10 Overall, there seems to be strong evidence
supporting a causal relationship; therefore, the use
of hypotonic fluid in maintenance intravenous
fluid therapy should be avoided.

Management
The management of seizures due to hyponatremia is the administration of 0.9% (normal) saline or
3% saline until the patient is seizure free. According
to Fleisher and Ludwig, the volume of 3% saline to
be administered can be calculated as follows:
10 mEq/L weight (kg) 0.6 or 10-12 mL/kg
over 1 hour. There are different opinions regarding
the continued use of 3% saline to obtain normal
sodium levels. Moritz's recommendations also
include the use of 3% saline to achieve an increase
of sodium levels by 20 to 25 mEq/L or to achieve a
serum sodium level of 125 to 130 mEq/L.9 Ray
recommends a more judicious approach, citing
successful outcomes with smaller increases in
serum sodium levels.20 The overall aim is to base
treatment on symptoms rather than the serum
sodium level. The utilization of 3% saline to stop
seizures due to hyponatremia is well accepted and
should also be considered if the patient has
symptoms consistent with cerebral edema. However,
the rate of correction should not exceed 0.5 mEq/
h once seizures are controlled to minimize the risk
of central pontine myelinosis.
In less symptomatic patients, the clinician must
try to determine if the hyponatremia is due to
dehydration, water intoxication, renal hyperconcentration states (ie, SIADH, adrenal insufficiency,

hypothyroidism, congestive heart failure, liver

failure, nephrotic syndrome, or intrinsic renal
disease) or due to hyperosmolar states such as
hyperglycemia or to pseudohyponatremic states
such as hyperlipidemia. The sodium correction for
hyperglycemia can be calculated as follows:
Corrected sodium = measured sodium
+ 0:016 serum glucose 100:
Obtaining serum and urine osmolarity will help
delineate between a renal hyperconcentration state
and water intoxication. In water intoxication, the
urine will be appropriately dilute. In renal hyperconcentration, the urine is not diluted despite the
presence of hyponatremia. In the context of SIADH,
the patient will be euvolemic with high urine
osmolality and sodium.9 In this case, fluid restriction will be the management of first choice unless
the patient has seizures, impaired consciousness, or
other severe symptoms or signs of hyponatremia.
Figure 2 provides one example of calculating the
deficit for the hypovolemic and hyponatremic
patient described in the case above. Again, the
most important point to understand is that these
calculations are merely rough estimations and that
patients will vary in terms of their actual rate of
correction. Therefore, it is imperative to closely
monitor serum electrolytes every 2 to 4 hours to
ensure judicious correction.

SUMMARY
Dysnatremias can be a diagnostic challenge for
pediatric emergency care providers because
patients can present with vague symptoms. It is
imperative that the ED physician consider the
etiology to direct treatment. Correction of a
dysnatremia should be judicious to avoid neurologic
sequelae. This article provides management examples for both hypernatremia and hyponatremia;
however, each patient will vary in the rate of his
or her correction so calculations are mere estimations. Emergency department physicians should
consult with a nephrologist if renal etiologies
are considered.

REFERENCES
1. Fleisher G, Ludwig S. Textbook of pediatric emergency
medicine. 4th ed. Philadelphia (Pa): Lippincott Williams and
Wilkins; 2000.
2. Moritz M, Manole M. Breastfeeding-associated hypernatremia:
are we missing the diagnosis? Pediatrics 2005;116:e343-7.
3. Unal S, Arhan E. Breast-feeding-associated hypernatremia:
retrospective analysis of 169 term newborns. Pediatr Int
2008;50:29-34.

278

VOL. 10, NO. 4 HYPERNATREMIA AND HYPONATREMIA / CHUNG AND ZIMMERMAN

4. Leung C, Chang WC. Hypernatremic dehydration due to

concentrated infant formula: report of two cases. Pediatr
Neonatol 2009;50:70-3.
5. Van Amerongen RH, Moretta AC. Severe hypernatremic
dehydration and death in a breast-fed infant. Pediatr Emerg
Care 2001;17:175-80.
6. Moritz M, Ayus J. Changing pattern of hypernatremia in
hospitalized children. Pediatrics 1999;104:435-9.
7. Robertson G, Carrhill M. Relationship between fluid management, changes in serum sodium and outcome in hypernatremia associated with gastroenteritis. Paediatr Child Health
2007;43:291-6.
8. Josepe N, Forbes G. Fluid and electrolytesclinical aspects.
Pediatr Rev 1996;17:395-403.
9. Moritz M, Ayus J. Disorders of water metabolism in children:
hyponatremia and hypernatremia. Pediatr Rev 2002;23:
371-80.
10. Moritz M, Ayus J. Preventing neurological complications from
dysnatremias in children. Pediatr Nephrol 2005;20:1687-700.
11. Roberts K. Fluid and electrolytes: parenteral fluid therapy.
Pediatr Rev 2002;22:380-7.
12. Farrer HC, Chande VT. Hyponatermia as the cause of seizures
in infants: retrospective analysis of incidence, severity and
clinical predictors. Ann Emerg Med 1995;26:42-8.
13. Lin CY, Tsau YK. Child abuse: acute water intoxication in a
hyperactive child. Acta Paediatr Taiwan 2005;46:39-41.
14. Tilelli JA, Ophoven JP. Hyponatremic seizures as a presenting symptom of child abuse. Forensic Sci Int 1986;2-3:213-7.

15. Arieff AI, Kronlund BA. Fatal child abuse by forced water
intoxication. Pediatrics 1999;103(6 Pt 1):1292-5.
16. Bruce RC, Kliegman RM. Hyponatremic seizures secondary to oral water intoxication in infancy: association
with commercial bottled drinking water. Pediatrics 1997;
100:E4.
17. Hoorn E, Geary D. Acute hyponatremia related to intravenous fluid administration in hospitalized children: an
observational study. Pediatrics 2004;113:1279-84.
18. Au A, Ray P. Incidence of postoperative hyponatremia and
complications in critically-ill children treated with hypotonic
and normotonic solutions. J Pediatr 2008;152:33-8.
19. Moritz M, Ayus J. Hospital acquired hyponatremiawhy are
hypotonic parenteral fluid still being used? Nephrology 2007;
3:374-82.
20. Ray P. Neurological complications from dysnatremias in
children: a different point of view. Pediatr Nephrol 2006;21:
1048-9.
21. Choong K, Kho ME. Hypotonic versus isotonic saline in
hospitalized children: a systematic review. Arch Dis Child
2006;91:828-35 [Epub 2006 Jun 5].
22. Yung M, Keely S. Randomised controlled trial of intravenous
maintenance fluids. J Paediatr Child Health 2009;45:9-14
[Epub 2007 Nov].
23. Jackson J. Risks of Intravenous administration of hypotonic
fluids for pediatric patients in ED and prehospital settings:
let's remove the handle from the pump. Am J Emerg Med
2000;18:269-70.